Our main aim in this project is to understand how mutations across many different domains of LRRK2 cause dominantly inherited Parkinsons disease. We have been particularly looking for shared effects of multiple mutations that are found in many different functional domains of the molecule. In the current period, we have followed up on our previous observations that LRRK2 interacts with two proteins at the trans-Golgi network (TGN), Rab7L1 and GAK. Interestingly, these two proteins are in loci for risk of sporadic Parkinson's disease. We have shown that all mutations in LRRK2 promote the retention of LRRK2 at the TGN. Ongoing work is aimed at understanding the mechanistic basis of this observation. We have no completed additional, secondary screens, that further nominate interactions between Golgi-derived vesicles and retromer particles, supporting further links to different familial forms of PD. We now have functional and mechanistic data that shows how mutations in LRRK2 affect vesicular transport in a bidirectional manner and thus describe a novel function for this protein that may be targeted for Parkinson's disease therapies in the future.